The general scientific goals of this project have changed dramatically owing to our discovery of an autosomal recessive mutation that causes severe combined immunodeficiency (SCID) in mice. The scid mutation occurred in the C.B-17 mouse strain. Affected mice (C.B-17scid) are severely deficient in both T and B lymphocytes. By means of adoptive transfer of fetal liver and bone marrow cells between C.B-17scid, BALB/c and (B6.C-9xBALB/c)F1 mice, we have shown that the scid mutation blocks the differentiation of lymphoid but not myeloid cells. The block, however, is not absolute, as some mice (approximately 15%) produce low levels of one or more Ig isotype. Also, in 5-\to 9-month-old C.B-17scid mice, we have detected a high incidence (greater than or equal to 10%) of spontaneous T-cell lymphomas which attest to the presence of early T cells. Our major aims are: (1)\to establish a colony of SFP C.B-17scid mice in a new, recently completed barrier facility; (2)\to further characterize the immunological status of C.B.-17scid mice; (3)\to understand why severe immune deficiency leads to T-cell lymphomas; and (4)\to try to correct the scid defect by genetic manipulation or by changes in cellular environment.